Canadian Neonatal Network Database Research Articles

Association of Shift-Level Organizational Factors with Nosocomial Infection in the Neonatal Intensive Care Unit

ObjectiveTo evaluate the association between shift-level organizational data (unit occupancy, nursing overtime ratios (OTRs), and nursing provision ratios (NPRs)) with nosocomial infection (NI) among very preterm infants in the Neonatal Intensive Care Unit (NICU). Study DesignMulticentre, retrospective cohort study, including 1921 infants 230–326 weeks’ gestation admitted to three tertiary-level NICUs in Quebec between 2014-2018. Patient characteristics and outcomes (NI) were obtained from the Canadian Neonatal Network database and linked to administrative data. For each shift, unit occupancy (occupied/total beds), OTR (nursing overtime hours/total nursing hours), and NPR (number of actual/number of recommended nurses) were calculated. Mixed-effect logistic regression models were used to calculate adjusted odds ratios (aOR) for the association of organizational factors (mean over 3 days) with the risk of NI on the following day for each infant. ResultsRate of NI was 11.5% (220/1921). Overall, median occupancy was 88.7% [interquartile range, IQR, 81.0-94.6], OTR 4.4% [IQR 1.5-7.6], and NPR 101.1% [IQR 85.5-125.1]. A higher 3-day mean OTR was associated with higher odds of NI (aOR 1.08, 95% CI 1.02-1.15), a higher 3-day mean NPR was associated lower odds of NI (aOR 0.96, 95% CI 0.95-0.98), and occupancy was not associated with NI (aOR, 0.99, 95% CI 0.96-1.02). These findings were consistent across multiple sensitivity analyses. ConclusionNursing overtime and nursing provision are associated with the adjusted odds of NI among very preterm infants in the NICU. Further interventional research is needed to infer causality.

Validation of a Costing Algorithm and Cost Drivers for Neonates Admitted to the Neonatal Intensive Care Unit.

Neonatal intensive care units (NICUs) account for over 35% of pediatric in-hospital costs. A better understanding of NICU expenditures may help identify areas of improvements. This study aimed to validate the Canadian Neonatal Network (CNN) costing algorithm for seven case-mix groups with actual costs incurred in a tertiary NICU and explore drivers of cost. A retrospective cohort study of infants admitted within 24 hours of birth to a Level-3 NICU from 2016 to 2019. Patient data and predicted costs were obtained from the CNN database and were compared to actual obtained from the hospital accounting system (Coût par Parcours de Soins et de Services). Cost estimates (adjusted to 2017 Canadian Dollars) were compared using Spearman correlation coefficient (rho). Among 1,795 infants included, 169 (9%) had major congenital anomalies, 164 (9%) with <29 weeks' gestational age (GA), 189 (11%) with 29 to 32 weeks' GA, and 452 (25%) with 33 to 36 weeks' GA. The rest were term infants: 86 (5%) with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia, 194 (11%) requiring respiratory support, and 541 (30%) admitted for other reasons. Median total NICU costs varied from $6,267 (term infants admitted for other reasons) to $211,103 (infants born with <29 weeks' GA). Median daily costs ranged from $1,613 to $2,238. Predicted costs correlated with actual costs across all case-mix groups (rho range 0.78-0.98, p < 0.01) with physician and nursing representing the largest proportion of total costs (65-82%). The CNN algorithm accurately predicts NICU total costs for seven case-mix groups. Personnel costs account for three-fourths of in-hospital total costs of all infants in the NICU. · Very preterm infants born below 33 weeks of gestation account for most of NICU resource use.. · Human resources providing direct patient care represented the largest portion of costs.. · The algorithm strongly predicted total costs for all case-mix groups..

65 Outcomes of Neonates Admitted to the NICU during the COVID-19 Pandemic: Comparison with a Pre-Pandemic Cohort

Abstract Introduction/Background The effect of the COVID-19 pandemic on neonatal outcomes is not yet completely understood. Objectives To compare the neonatal outcomes of very preterm infants admitted to Canadian NICUs pre- and during the COVID-19 pandemic. Design/Methods This retrospective cohort study included infants born &amp;lt;33 weeks and admitted to tertiary Canadian NICUs participating in the Canadian Neonatal Network (CNN) database. The sample included 14,368 infants from two cohorts: 7,280 infants pre-pandemic (April 1, 2018 – December 31, 2019) and 7,088 infants during the pandemic (April 1, 2020 – December 31, 2021). Primary composite outcomes were mortality or major morbidity. Care practices and interventions were compared. Relative risk (RR) comparing the pandemic vs pre-pandemic periods were estimated using generalized estimated equations and adjusted for confounders. Results The characteristics of infants admitted before and during the pandemic were not significantly different. The incidence of mortality or major morbidity was similar pre- and during the pandemic (37%, 36% respectively; RR=1.01 [0.92, 1.01]; Table 1). Infant health outcomes were not significantly different between periods. There was a non-significant decrease in the exclusive receipt of mothers’ own milk (MOM) at discharge (45% pre- and 37% during; RR=0.85 [0.68, 1.06]). Conclusion There was no difference in clinical outcomes between pre-pandemic and pandemic cohorts. The possibility of lower receipt of exclusive MOM at discharge during the COVID-19 pandemic needs further study.

71 Trends, Practice Patterns, and Opportunities for Improvement in Postnatal Steroids Use for Bronchopulmonary Dysplasia – Eleven Years Observational Study

Abstract Background Postnatal steroids (PNS) use in preterm infants improves pulmonary function in a select subset of patients but can potentially increase the risk of spontaneous intestinal perforation and cerebral palsy. Despite national guidelines, reducing intra-centre variation and demonstrating responsible stewardship in PNS use have been challenging. Objectives To describe (i) PNS type, regimen, time of initiation, use over time, and identify opportunities for improving practices in the use of PNS for bronchopulmonary dysplasia (BPD); (ii) outcome at discharge for infants who received PNS. Design/Methods We conducted a retrospective observational study in a quaternary NICU that included infants born at &amp;lt;33 weeks gestational age who received PNS to prevent or treat BPD between 2011 and 2021. We initially identified all infants who received PNS from the pharmacy registry, followed by demographic, PNS use details, and outcome data collection from the Canadian Neonatal Network (CNN) database, discharge summaries and, occasionally, by reviewing individual charts. Results The mean (SD) gestational age and birth weight of 184 eligible infants were 25(24-26) weeks and 720(625-841) grams respectively. Based on timing of first course of PNS, 2(1.1%), 93(50.5%), 85(46.2%), and 4(2.2%) infants received PNS in early (E) (&amp;lt; 7 days), early evolving (EE) (7-28 days), late evolving (LE) (29 days – 36 + 6 weeks PMA), and established (Es) (≥ 37 weeks) phases, respectively. 157 (85.3%) infants received dexamethasone and 22 (12%) received hydrocortisone as the first PNS course. Infants in the EE group, when compared with the LE group, received more days and higher cumulative dose of PNS 13(10-28) vs. 10(10-16) p= 0.04, and 24(24-60) vs. 24(24-25) hydrocortisone equivalents in milligrams/kilograms, p=0.01, respectively. Two common regimens used at our centre were 10-day Dexamethasone: A Randomized Trial (DART) and 22-day tapering doses of hydrocortisone (STOP-BPD). Deviation from published protocols based on duration (±20%), dose (±10%) or timing was 66.7% and 33.3% with hydrocortisone and dexamethasone use. Dexamethasone usage remained stable, but a small increase in hydrocortisone use and the cumulative PNS dose received occurred over time. Survival, survival without major morbidity, moderate to severe BPD, and technology dependence at discharge were 87%, 1.6%, 90.8% and 66.9%, respectively. Identified opportunities for improvement were: adapting national guidelines to local context, creating order sets to reduce deviations, and using this study’s outcomes during PNS decision-making conversations with family. Conclusion Variation in the use of hydrocortisone was higher than for dexamethasone, and cumulative dose received per infant increased over time. Potential interventions to reduce variation in PNS use and optimize decision- making were identified.

Incidence and risk factors for autism spectrum disorder among infants born

This study was aimed to assess the incidence of and risk factors for autism spectrum disorder (ASD) among preterm infants born <29 weeks' gestational age (GA). A retrospective cohort study of infants born <29 weeks' GA admitted to two tertiary neonatal intensive care units (2009 to 2017) and followed ≥18 months corrected age (CA) at a neonatal follow-up clinic. The primary outcome was ASD, diagnosed using standardized testing or provisional diagnosis at ≥18 months CA. Patient data and 18-month CA developmental outcomes were obtained from the local Canadian Neonatal Follow Up Network database and chart review. Stepwise logistic regression assessed factors associated with ASD. Among 300 eligible infants, 26 (8.7%) were diagnosed with confirmed and 21 (7.0%) with provisional ASD for a combined incidence of 15.7% (95% confidence interval [CI] 11.7 to 20.3). The mean follow-up duration was 3.9 ± 1.4 years and the mean age of diagnosis was 3.7 ± 1.5 years. Male sex (adjusted odds ratio [aOR] 4.63, 95% CI 2.12 to 10.10), small for gestational age status (aOR 3.03, 95% CI 1.02 to 9.01), maternal age ≥35 years at delivery (aOR 2.22, 95% CI 1.08 to 4.57) and smoking during pregnancy (aOR 5.67, 95% CI 1.86 to 17.29) were significantly associated with ASD. Among ASD infants with a complete 18-month CA developmental assessment, 46% (19/41) had no neurodevelopmental impairment (Bayley-III<70, deafness, blindness, or cerebral palsy). ASD is common among infants born <29 weeks' GA and possibly associated with identified risk factors. Such findings emphasize the importance of ASD evaluation among infants <29 weeks' GA and for continued reporting of developmental outcomes beyond 18-months of corrected age.

Neonatal outcomes of twins &lt;29 weeks gestation of mothers with hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown. Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infants &lt;29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers. Of the 2414 eligible twin infants &lt;29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59). Preterm twin infants born to mothers with HDP also had higher odds of mortality (AOR 2.02, 95% CI 1.23-3.32). There was no difference in other outcomes. Preterm twin infants &lt;29 weeks gestation of HDP mothers have higher odds of severe ROP and mortality. Hypertensive disorders of pregnancy, associated with placental dysfunction, are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality.

The Trend in Costs of Tertiary-Level Neonatal Intensive Care for Neonates Born Preterm at 220/7-286/7 Weeks of Gestation from 2010 to 2019 in Canada

To describe the trend in costs over 10years for tertiary-level neonatal care of infants born 220/7-286/7weeks of gestation during an ongoing Canadian national quality improvement project. Clinical characteristics, outcomes, and third-party payor costs for the tertiary neonatal care of infants born 220/7-286/7weeks of gestation between the years 2010 and 2019 were analyzed from the Canadian Neonatal Network database. Costs were estimated using resource use data from the Canadian Neonatal Network and cost inputs from hospitals, physician billing, and administrative databases in Ontario, Canada. Cost estimates were adjusted to 2017 Canadian dollars (CAD). A generalized linear mixed-effects model with gamma regression was used to estimate trends in costs. Between 2010 and 2019, the number of infants born <24weeks of gestation increased from 4.4% to 7.7%. The average length of stay increased from 68days to 75days. Unadjusted average±SD total costs per neonate were $120 717±$93 062 CAD in 2010 and $132 774±$93 161 CAD in 2019. After adjustment for year, center, and gestation, total costs and length of stay increased significantly, by $13 612 CAD (P<.01) and 8.1days (P<.01) over 10years, respectively; whereas costs accounting for LOS remained stable. The total costs and length of stay for infants 220/7-286/7weeks of gestation have increased over the past decade in Canada during an ongoing national quality improvement initiative; however, there was an increase in the number and survival of neonates at the age of periviability.

Risk factors for neonatal thrombosis: A retrospective study conducted in a single Canadian intensive care unit

Among children, neonates have the highest incidence of thrombosis. We conducted a retrospective review of neonatal thrombosis, in a single intensive care unit (ICU) over 4.5 years. Among 4860 ICU admissions to our center, identified through the Canadian Neonatal Network database, 186 were associated with arterial and venous thrombosis involving 195 thrombotic sites. The neonatal thrombosis incidence was 38 per 1000 neonatal ICU admissions. We assessed patient characteristics and compared the association between risk factors and thrombosis. In the multivariate analysis, central venous catheters, sepsis, and respiratory distress syndrome were significant predictors of neonatal thrombosis.

Association of Weight Changes by Three Days after Birth and Mortality and/or Severe Neurological Injury in Preterm Infants < 29 Weeks Gestational Age: A Multicenter Cohort Study.

Objective: This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants <29 weeks gestational age (GA). Study design: This multicenter retrospective cohort study employed data from the Canadian Neonatal Network database. The primary outcome was a composite of mortality and/or severe neurological injury. Multivariable quadratic and linear regression models which adjusted for potential confounders were built. Results: A total of 9275 preterm infants (median GA 26, IQR 25, 28 weeks) were included. The optimal weight change range at day three, after adjustment for potential confounders for the primary outcomes, was −15 to −8.9%. Conclusions: There is a ‘U’-shaped relationship between weight change from birth to day three and mortality and/or severe neurological injury. Interventional studies, which target weight loss within the range found in this study and evaluate the impact on neonatal outcomes, are needed to corroborate our findings.

Determining the Effect of Birth Weight on Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy.

We examine the effect of birth weight (BW) for gestational age (GA) on the temperatures reached during the treatment of neonatal hypoxic-ischemic encephalopathy (HIE) with therapeutic hypothermia (TH). Retrospective data of 1,736 neonates with HIE who received TH were extracted from the Canadian Neonatal Network database for neonates admitted from 2010 to 2017. Neonates were stratified into three BW groups: small for GA < 10th centile, large for GA > 90th centile, and according to GA 10th to 89th centile at a given gestation using Canadian population data norms. There was no significant difference in the lowest temperature reached, the likelihood of overshooting temperatures < 32.5°C during TH, or the change of encephalopathy stages among the three groups. BW for GA did not appear to influence the temperatures neonates reached during hypothermia or encephalopathy stage following TH. · Therapeutic hypothermia is well tolerated irrespective of weight for age. · SGA infants achieved and maintained target temperature similar to AGA and LGA babies. · Change in the Sarnat stage after hypothermia was similar across all birth weight groups.

84 Looking back to move forward; can fetal placental inflammatory response play a role in risk of sepsis and clinical decision making in preterm infant

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Sepsis adversely impacts the survival of very low birth weight infants (VLBW), with a mortality risk up to 50%. Its diagnosis in premature infants is challenging. Conversely, prolonged antibiotic use is associated with perilous potential consequences, propelling the need to better identify those at risk of sepsis. The presence of a histological intra-amniotic inflammation (IAI) response may be associated with an increased risk of early onset sepsis (EOS). Currently, it is unknown how the diagnosis of histological IAI impacts the risk of sepsis. Objectives Our research goal is to explore histological fetal and maternal inflammation in the placenta in VLBW infants and to evaluate if specific recommendations about antibiotic management of VLBW infants with histological fetal response can be proposed. Design/Methods Retrospective cohort study of all infants &amp;lt; 1500 g born to a mother with histologically confirmed IAI. Demographic information about the pregnancy, delivery and postnatal course up to 28 days of life was extracted. Descriptive statistical analysis was conducted to compare the characteristics of infants with histological fetal response using χ2 test or Fisher’s exact test and Wilcoxon rank sum test or ANOVA. Results Seventy-three mother-baby pairs were reviewed. EOS prevalence (19%) in our IAI group of VLBW infants is much higher than EOS observed in all VLBW infants from the Canadian Neonatal Network database (below 3%). In our cohort, the majority had fetal inflammatory stage 1 (31.6%) and fetal inflammatory grade 0 (50%). There was no statistically significant distribution amongst the fetal stages or grades. Time to sepsis event analysis showed that the earlier fetal inflammatory grade was associated with positive cultures occurring earlier, while in the later grades there demonstrated longer latency to positive cultures. This trend was also true when looking at the maternal inflammatory stages. Nine infants who had antibiotics discontinued from day of life (DOL) 2-5 developed a positive blood culture ≤ DOL8. Conclusion Our results suggest that the presence of mild fetal inflammatory changes is associated with earlier positive cultures. We hypothesize that later grades may be associated with longer infection exposure leading to prolonged maternal antibiotics, resulting in less EOS. Majority of positive cultures were within the 3-8 day window, suggesting a role of knowing the fetal inflammatory response when deciding duration of antibiotic treatment.

93 Timing and frequency of head ultrasound screening to identify severe neurological injury among very preterm infants

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Universal head ultrasound (HUS) screening for severe neurological injury (SNI) injury is recommended for infants born &amp;lt; 32 weeks’ gestational age (GA). However, the risk of SNI varies inversely with GA at birth and other known risk factors; therefore targeted screening may be more appropriate. Objectives The objective of the study is to develop a risk-stratified HUS screening protocol for infants born &amp;lt; 32 weeks’ to identify SNI accurately while minimizing resource use. Design/Methods Retrospective cohort study of infants born 23-31 weeks’ admitted to a tertiary NICU between 2011-2017. Patient characteristics were extracted from the Canadian Neonatal Network database. All HUS were individually reviewed by a trained abstractor and grouped based on date of exam relative to birth: ≤ 3 days, 4-7 days, 8-14 days, 28-42 days and 35-42 weeks’ corrected GA. Severe neurological injury was defined as intraventricular hemorrhage grade ≥ 3 and/or periventricular leukomalacia on HUS. Logistic regression models were used to identify perinatal risk factors for SNI and determine the number and timing of HUS with highest diagnostic accuracy. Results Of 651 infants included, 72 (11%) developed SNI. Independent risk factors for SNI were GA &amp;lt;29 weeks (AOR 3.09, 95% CI 1.65-6.08), vasopressors (AOR 2.95, 95% CI 1.24-6.80) and mechanical ventilation on day of admission (AOR 2.22, 95% CI 1.23-4.11). Infants were grouped into three screening groups based on their exposure to these risk factors (Table 1). Diagnostic accuracy of 63 models of combinations of HUS time points were assessed, and a screening protocol was developed based on the specific time points of HUS that maximized diagnostic accuracy (area under the ROC curve &amp;gt;0.9) while minimizing number of HUS for each screening group (Table 2). Using this protocol could reduce the total number of HUS performed by 920 (40%) and median number of HUS per infant from three (IQR 2-4) to 2 (IQR 1-2; p &amp;lt; 0 .001). Conclusion Implementation of a risk factor-based HUS screening protocol may reduce resource use while maintaining high diagnostic accuracy for SNI, and reflects choosing wisely in the NICU.

67 Are NICUs too busy?

Abstract Primary Subject area Neonatal-Perinatal Medicine Background In a health care system with limited resources, hospital organizational factors such as unit occupancy and nurse-to-patient ratios may contribute to patient outcomes. Objectives We aimed to assess the association of NICU occupancy and nurse staffing with outcomes of very preterm infants born &amp;lt; 33 weeks gestational age (GA). Design/Methods This was a multicenter retrospective cohort study of infants born 23-32 weeks GA without major congenital anomaly, admitted within 2 days after birth to one of four Level 3 NICUs in Quebec, Canada (2015-2018). For each 8 h shift, data on unit occupancy were obtained from a central provincial database (SiteNeo) and linked to the hospital nursing hours database (Logibec). Unit occupancy rates and nursing provision ratios (nursing hours/recommended nursing hours based on patient dependency categories) were pooled for the first shift, 24 h, and 7 days of admission for each infant. Patient data were obtained from the Canadian Neonatal Network database. Primary outcome was mortality and/or morbidity (severe neurological injury, bronchopulmonary dysplasia, necrotizing enterocolitis, and late-onset sepsis, severe retinopathy of prematurity). Adjusted odds ratios (AOR) for association of exposure with outcomes were estimated using generalized linear mixed models with a random effect for center, while adjusting for confounders (gestational age, small for gestational age, sex, outborn, Score for Neonatal Acute Physiology version 2, mode of delivery, and the other organizational variables). Results Among 1870 infants included in analyses, 796 (43%) had mortality/morbidity. Median occupancy was 89% (IQR 82-94) and median nursing provision was 1.13 (IQR 0.97-1.37). Overall higher NICU occupancy on shift of admission, first 24 h, and 7 days were associated with higher odds of mortality/morbidity (Figure 1) but nursing provision was not (Figure 2). Subgroup analysis by GA (&amp;lt; 29 and 29-32 weeks) yielded similar results (not shown). Generalized linear mixed model analyses showed that a 5% reduction in occupancy in the first 24 h of admission was associated with a 6% reduction in mortality/morbidity. Conclusion NICU occupancy is associated with mortality/morbidity among very preterm infants and may reflect lack of adequate resources in periods of high activity. Interventions aimed at reducing occupancy and maintaining adequate resources need to be considered as strategies to improve patient outcomes.

87 Validation of a Costing Algorithm in the Neonatal Intensive Care Unit and Identification of Cost Drivers for Neonates

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Neonatal Intensive Care Units (NICUs) account for over 35% of pediatric in-hospital clinical costs, thus implying that a better understanding of care expenditures within these units is the first step for improving efficiency of care. The Canadian Neonatal Network (CNN) algorithm is the first to provide case-specific costs based on resource usage among preterm infants born &amp;lt; 37 weeks but has not yet been validated for other populations in the NICU. Objectives To validate the CNN costing algorithm in six case-mix categories with real-time costs obtained from hospital-specific financial software (CPSS) in a tertiary-level NICU and assess the variations in proportion of cost centers across case-mixes. Design/Methods A retrospective cohort study of all patients admitted within 24h of birth to a Level 3 medico-surgical NICU 2016-2019. Patient demographics, clinical information and CNN predicted costs were obtained from the CNN database. Real-time costs were obtained from the hospital financial software (CPSS). Total and daily costs were compared between sources using Pearson correlation coefficient (r) and paired Student’s t-test. Costs were adjusted to account for inter-institutional and -provincial price variations using the Cost of Standard Hospitalization Stay from the Canadian Institute for Health Information. Proportions of each cost center across the different case-mix categories were compared using Chi-square analyses. Results Among the 1795 live infants admitted into the NICU, 167 (9.3%) were &amp;lt; 29 weeks gestational age (GA), 193 (11%) were 29-32 weeks GA, 457 (25.5%) were 33-36 weeks GA, 144 (8%) had major congenital anomalies, 179 (10%) were term infants diagnosed with Hypoxic-Ischemic Encephalopathy (HIE) and 672 (37%) were term infants with no HIE or major congenital anomalies. Median NICU costs varied according to each case-mix from $10,025 for term infants without HIE or congenital anomaly to $180,145 for infants born &amp;lt; 29 weeks (Figure 1). Despite high variation in total NICU costs, there were small variations in median daily costs (range: $1,312-$1,941). Overall, the CNN algorithm strongly correlated with CPSS total costs across all 6 case-mix categories (r range 0.90-1.00, p-value &amp;lt; 0 .01) (Figure 2). We report a consistent strong predictive performance of the algorithm in 5/8 pre-specified cost centers among preterm infants (r range 0.77-0.99, p-value &amp;lt; 0 .01). Unit producing personnel (nurses and physicians) consistently comprised the largest proportion of total costs (64-78%) for all case-mix categories. Conclusion The CNN algorithm accurately predicts NICU total costs for six case-mix categories. Costs per day were comparable across different case-mix categories, and unit producing personnel represented the highest proportion of costs suggesting that reductions in length of stay would be the most efficient method to reduce NICU costs.

74 Central venous line-related thrombosis in neonates: A population-based study

Abstract Primary Subject area Neonatal-Perinatal Medicine Background The incidence of central venous line (CVL)-related thromboembolism (TE) in neonates is rising dramatically. The mainstay of treatment in neonatal thrombosis is anticoagulant therapy. However, management of neonatal CVL-related TE is particularly complex, as the higher risk of systemic and intracranial bleeding, especially in premature babies, must be balanced with the thrombotic risks, including death, or morbidity such as organ dysfunction, post-thrombotic syndrome, and neurodevelopmental sequelae. There is a paucity of evidence regarding the epidemiology of neonatal CVL-related thrombosis, to help clinicians identify neonates at high-risk of CVL-related thrombosis, as well as to tailor treatment based on the risks and benefits of anticoagulants in neonates. Objectives The objectives of this retrospective cohort study are: 1) to determine the main risk factors of CVL-related TE in neonates admitted to the neonatal intensive care unit (NICU); and 2) to compare the effectiveness and safety between different antithrombotic treatment modalities for neonatal CVL-related TE using the Canadian Neonatal Network (CNN) database and electronic medical chart review. Design/Methods Neonates ≤ 28 days of life admitted to the NICU for ≥ 24 hours requiring a CVL with TE confirmed by imaging were included in the study. The main effectiveness outcome is the resolution of TE, whereas the main safety outcome is the apparition of a major bleeding. In this study (n=39), we compared the effectiveness and safety outcomes according to antithrombotic treatment modalities (conservative vs. anticoagulation). Results The median gestational age is 35[26-38] weeks, and the mean birth weight is 2096±1110 g. CVL responsible for TE was umbilical venous catheter (28%), umbilical arterial catheter (46%), peripherally inserted central catheter (PICC line) (8%), and peripheral arterial catheter (18%). The anticoagulation therapy is more effective to achieve a partial and complete resolution of TE than the conservative treatment after a mean follow-up of 7 weeks (p=0.02). However, there were no differences according to antithrombotic treatment group regarding safety outcome assessed by major bleedings (p=0.2). Conclusion Our results tend to suggest that anticoagulation therapy is more effective to achieve resolution of CVLs-related TE than conservative treatment without compromising the safety of neonates. However, a large multicentric study is required to evaluate the risks and benefits of anticoagulants in neonates.

72 Identifying Perinatal and Neonatal Factors Associated with Autism Spectrum Disorder among Preterm Infants Born &lt; 29 Weeks’ Gestation

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Preterm infants born &amp;lt;29 weeks’ gestational age (GA) are at risk for autism spectrum disorder (ASD), typically diagnosed at age &amp;gt;2 years. Perinatal and neonatal factors, including interventions and morbidities during neonatal intensive care unit admission, may contribute to the risk of ASD among these infants. Objectives We aimed to assess the incidence of and risk factors for, ASD among preterm infants born &amp;lt; 29 weeks’ GA. Design/Methods &amp;lt;29 weeks’ GA admitted 2009-2017 to two tertiary NICUs and followed ≥18 months at the Neonatal Follow-Up Clinic. Primary outcome was ASD defined as a confirmed diagnosis using standardized testing or suspected diagnosis at &amp;gt;18 months of corrected age. Patient data and 18-month developmental outcomes were obtained from the local Canadian Neonatal Follow Up Network database and from chart review. Stepwise logistic regression was used to identify significant perinatal, neonatal, and socio-economic factors associated with ASD. Results Among 300 eligible infants, 47 (15.7%) developed ASD (Figure 1, Table 1). Mean follow-up duration was 3.9 ± 1.4 years and mean age at diagnosis was 3.7 ± 1.5 years. Male sex (adjusted odds ratio [aOR] 4.63, 95% CI 2.12, 10.10), small for gestational age status (aOR 3.03, 95% CI 1.02, 9.01), maternal age ≥ 35 years at delivery (aOR 2.22, 95% CI 1.08, 4.57), and tobacco use in utero (aOR 5.67, 95% CI 1.86, 17.29) were significantly associated with ASD. Major neonatal morbidities (retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, late-onset sepsis, severe neurological injury) were not associated with ASD. Among infants with a complete 18-month corrected age developmental assessment and later diagnosed with ASD, 46% (19/41) did not have significant neurodevelopment impairment (Bayley-III &amp;lt; 70, deafness, blindness, or cerebral palsy). Conclusion ASD is a significant morbidity among infants born &amp;lt; 29 weeks’ GA. ASD was associated with infant and prenatal risk factors but not with neonatal morbidities or socio-economic factors. These findings emphasize the need for ASD evaluation among preterm infants &amp;lt; 29 weeks and for reporting developmental outcomes beyond 18-months corrected age.

63 Characterizing Organizational Risk Factors and Clinical Impacts of Unplanned Extubations among Infants in the Neonatal Intensive Care Unit

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Organizational factors in neonatal intensive care units (NICUs) can increase the risk of adverse events, such as unplanned extubations (UPEs). UPE is the premature and unanticipated removal of an endotracheal tube. UPE and subsequent reintubation may increase the risk for lung injury and bronchopulmonary dysplasia (BPD) among preterm infants. Objectives First, we aimed to assess the association between daily nursing overtime and UPEs in the NICU. Second, we aimed to evaluate the association between UPE, re-intubation after UPE, and BPD in the sub-group of infants born &amp;lt; 29 weeks’ gestational age (GA). Design/Methods We conducted a retrospective cohort study including infants admitted to a tertiary care NICU between 2016-2019. Daily nursing hours were obtained from local administrative databases. Patient data was collected from the local Canadian Neonatal Network database. Association between ratio of daily nursing overtime hours/total nursing hours (OTR) was compared between days with and without UPEs, using logistic regression analyses. Associations between UPE and BPD among infants born &amp;lt;29 weeks requiring mechanical ventilation was evaluated in a 1:1 propensity-score matched (PSM) cohort. Infants were matched based on GA ± 2 weeks, mechanical ventilation days at time of UPE ± 5 days and SNAPII&amp;gt;20. Results There were 108/1370 (7.8%) days with ≥ 1 UPE, for a total of 116 UPE events from 87 patients (23-42 weeks GA). Higher median OTR was observed on days with UPE compared to days without (3.3% vs. 2.5%, p=0.01). OTR was associated with higher adjusted odds of UPE (aOR 1.09, 95% CI 1.01-1.18), while other organizational variables were not (Table 1). Among ventilated infants &amp;lt;29 weeks’ GA (n=XX), UPE rate was 31% (59), BPD rate was 42% (81) and re-intubation rate after UPE was 59% (35). In the PSM cohort of infants &amp;lt;29 weeks, re-intubation after UPE, was associated with increased length of mechanical ventilation (aOR 16.45; CI 6.18, 26.72) as well as increased odds of BPD, when compared to infants not requiring re-intubation (aOR 4.97, 95% CI 1.54-18.27) (Table 2). Conclusion Higher nursing overtime was associated with increased UPEs in the NICU. Re-intubation was frequently required after a UPE. Among the infants born &amp;lt; 29 weeks’ GA, UPE requiring reintubation was associated with increased total length of mechanical ventilation and increased risk of BPD. Our findings highlight the role of workforce management in improving outcomes in the NICU, through reducing the incidence of UPEs.

50 Poractant alfa versus bovine lipid extract surfactant for respiratory distress syndrome in preterm infants: A prospective comparative effectiveness cohort study

Abstract Primary Subject area Neonatal-Perinatal Medicine Background There is a paucity of comparative effectiveness data for bovine lipid extract surfactant (BLES) and poractant alfa (Curosurf). Objectives To compare duration of respiratory support and short-term outcomes in very preterm infants treated with bovine lipid extract surfactant and poractant alfa. Design/Methods We performed a prospective, multicentre, comparative effectiveness study. Thirteen Canadian level III neonatal intensive care units (NICUs) provided bovine lipid extract surfactant to infants born &amp;lt;32 weeks’ gestational age (GA) for a set period of time in the year 2019 (3 to 9 months), then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support (invasive and non-invasive). We utilized the Canadian Neonatal Network database for all study data. Results A total of 968 eligible infants (530 infants &amp;lt; 28 weeks’ GA and 438 infants 280-316weeks’ GA) were included, of which 494 received bovine lipid extract surfactant and 474 received poractant alfa. In unadjusted analysis, no difference was observed in total duration of any respiratory support (median 38 vs. 40.5 days). After adjusting for baseline characteristics and accounting for cluster effects, infants treated with poractant alfa spent a median of 4.16 fewer days on respiratory support (95% CI 0.05, 8.28 days). This reduction was observed in the subgroup of infants 280-316 weeks’ GA, but not in those &amp;lt; 28 weeks’ GA, and was explained by their shorter time on non-invasive respiratory support. No differences were observed in the need to re-dose surfactant, hospital mortality, bronchopulmonary dysplasia, or length of stay in NICU. Conclusion Administration of poractant alfa was associated with shorter median duration of respiratory support compared to bovine lipid extract surfactant in preterm neonates &amp;lt; 32 weeks’ GA.

60 Impact of sequential implementation of a standardized feeding protocol and donor breastmilk on necrotizing enterocolitis among preterm infants born &amp;lt;31 weeks gestation

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality among preterm infants born &amp;lt;31 weeks. Nutritional interventions such as a standardized feeding protocol (SFP) and donor breastmilk (DBM) are recommended to reduce NEC. Objectives Our objective was to assess the impact of implementing a feeding protocol and pasteurized donor breastmilk protocol on NEC among preterm infants born &amp;lt; 31 weeks GA. Design/Methods Retrospective cohort study including 682 infants born &amp;lt; 31 weeks, who survived ≥ 14 days and were admitted to two tertiary NICUs from 2009-2018. Data was obtained from the local Canadian Neonatal Network database. Infants were classified into epochs, based on the timing of interventions: Epoch 1, baseline (2009-2012); Epoch 2, SFP (2013-2015); Epoch 3, SFP + DBM (2016-2018). The primary outcome was NEC stage ≥ 2. Multivariable logistic regression models were used to assess associations between epochs and outcomes and were adjusted for confounders. Results Among 682 infants, 46 (7%) had NEC and 74 (11%) had mortality/NEC. Rates of NEC decreased with each epoch: 10% (25/246) Epoch 1 (baseline); 5% (8/163) Epoch 2 (SFP); and 5% (13/273) Epoch 3 (SFP+DBM), (p&amp;lt;0.01) (Table1). SFP alone was associated with significantly lower odds of NEC compared to baseline (Epoch 2 vs 1, AOR 0.42, 95% CI 0.17-0.93) (Table 2). Implementation of DBM was not associated with lower odds of NEC compared to SFP alone (Epoch 3 vs 2, AOR 0.94, 95% CI 0.38-2.42) (Table2). Number of NPO days prior to the initiation of enteric feeds after birth decreased in Epoch 3 (Epoch 1&amp;2: 2 days versus Epoch 3: 1 day; p&amp;lt;0.01). Exclusive human breastmilk feeds during the first 3 weeks increased from 62% in Epoch 2 to 82% in Epoch 3 (p&amp;lt;0.01). A significant decrease in number of total parenteral nutrition and central venous line (CVL) days was observed from Epoch 1 to 3 (25 to 15 days and 26 to 15 days respectively; p&amp;lt;0.01) (Table 1), this was reflected in the decrease in late onset sepsis (Epoch 3 vs 1, AOR 0.55, 95% CI 0.35-0.86). Conclusion Implementation of SFP was associated with a significant decrease in NEC among infants born &amp;lt; 31 weeks. Combining the SFP and DBM did not further decrease NEC, but was associated with shorter NPO days, higher exclusive human breastmilk exposure, and significant decrease in number of central venous line (CVL) days.

Costs of Neonatal Intensive Care for Canadian Infants with Preterm Birth

To develop and validate an itemized costing algorithm for in-patient neonatal intensive care unit (NICU) costs for infants born prematurely that can be used for quality improvement and health economic analyses. We sourced patient resource use data from the Canadian Neonatal Network database, with records from infants admitted to 30 tertiary NICUs in Canada. We sourced unit cost inputs from Ontario hospitals, schedules of benefits, and administrative sources. Costing estimates were generated by matching patient resource use data to the appropriate unit costs. All cost estimates were in 2017 Canadian dollars and assigned from the perspective of a provincial public payer. Results were validated using previous estimates of inpatient NICU costs and hospital case-cost estimates. We assigned costs to 27 742 infants born prematurely admitted from 2015 to 2017. Mean (SD) gestational age and birth weight of the cohort were 31.8 (3.5) weeks and 1843 (739) g, respectively. The median (IQR) cost of hospitalization before NICU discharge was estimated as $20 184 ($9739-51 314) for all infants; $11 810 ($6410-19 800) for infants born at gestational age of 33-36weeks; $30 572 ($16 597-$51 857) at gestational age of 29-32weeks; and $100 440 ($56 858-$159 3867) at gestational age of <29weeks. Cost estimates correlated with length of stay (r=0.97) and gestational age (r=-0.65). The estimates were consistent with provincial resource estimates and previous estimates from Canada. NICU costs for infants with preterm birth increase as gestation decreases and length of stay increases. Our cost estimates are easily accessible, transparent, and congruent with previous cost estimates.